The technical field of this invention concerns medical devices useful for the repair of severed nerves and methods for fabricating and using such devices for nerve repair.
The problem of repairing severed nerves is a long-standing one that has plagued surgeons for over a hundred years. Despite advances in microsurgical techniques, a patient's recovery from a serious wound is often limited by a degree of nerve damage which cannot be repaired. The replanting of amputated fingers and limbs is especially limited by poor nerve regeneration.
When a nerve is severed, the functions supplied by that nerve, both motor and sensory, are lost. The appendages of the nerve cells (neurites or axons) in the distal regions of the severed nerve, or those areas furthest from the spinal cord, degenerate and die, leaving only the sheaths in which they were contained. These, too, degenerate with time. The axons in the proximal stump that remain connected to the spinal cord or dorsal root ganglion also suffer some degeneration.
However, degeneration generally does not proceed to the death of all of the nerve cell bodies. Moreover, if the injury occurs far enough from the nerve cell bodies, regeneration will occur. Regeneration of nerves does not normally include proliferation of nerve cells; rather, the injured nerve cell will grow "sprouts" from the tip of its severed axon (or nerve cell process). These axonal sprouts extend and grow distally and attempt to reenter the intact neurilemmal sheaths of the distal portion of the severed nerve. If entry is successfully made, axonal growth will continue down these sheaths, and function will eventually be restored.
In the conventional approach to nerve repair, an attempt is made to align the cut ends of the fascicles (nerve bundles within the nerve trunk). A similar approach is taken with smaller nerves. In either case, the chief hazard to the successful repair is the trauma produced by the manipulation of the nerve ends and the subsequent suturing to maintain alignment. The trauma appears to stimulate the growth and/or migration of fibroblasts and other scar-forming, connective tissue cells. The scar tissue prevents the regenerating axons in the proximal stump from reaching the distal stump to reestablish a nerve charge pathway. The result is a permanent loss of sensory or motor function.
Various attempts have been made over the years to find a replacement for direct (i.e., nerve stump-to-nerve-stump) suturing. Much of the research in this field has focused on the use of "channels" or tubular prosthesis which permit the cut ends of the nerve to be gently drawn into proximity and secured in place without undue trauma. It is also generally believed that such channels can also prevent, or at least retard, the infiltration of scar-forming, connective tissue.
For example, the use of silastic cuffs for peripheral nerve repair was reported by Ducker et al. in Vol. 28, Journal of Neurosurgery. pp. 582-587 (1968). Silicone rubber sheathing for nerve repair was reported by Midgley et al. in Vol. 19, Surgical Forum, pp. 519-528 (1968) and by Lundborg et al. in Vol. 41, Journal of Neuropathology in Experimental Neurology. pp. 412-422 (1982). The use of bioresorbable polyglactin mesh tubing was reported by Molander et al. in Vol. 5, Muscle & Nerve. pp. 54-58 (1982). The use of semipermeable acrylic copolymer tubes in nerve regeneration was disclosed by Uzman et al. in Vol. 9, Journal of Neuroscience Research. pp. 325-338 (1983). Bioresorbable nerve guidance channels of polyesters and other polymers have been reported by Nyilas et al. in Vol. 29, Transactions Am. Soc. Artif. Internal Organs. pp. 307-313 (1983) and in U.S. Pat. No. 4,534,349 issued to Barrows in 1985.
Despite the identification of various materials which can serve as nerve guidance channels, the results of research to date have revealed significant shortcomings in such prosthesis. For example, some of the materials identified above have lead to inflammatory reactions in the test animals, and have failed to exclude scar tissue formation within the channels. The total number of axons, the number of myelinated axons, the thickness of the epineurial, and the fascicular organization of nerves regenerated within guidance channels are all typically less than satisfactory and compare poorly with the original nerve structure of the test animals. Moreover, the loss of sensory or motor function is still the most common outcome of such laboratory experiments.
Electrical currents (such as DC stimulation or the application of pulsed electrical currents) directly applied to a nerve have been reported to enhance regeneration in experimental animals. For example, electrical currents produced by electrode cuffs, connected to an extracorporeal power source, and fitted to a silicone channel, have been tried to enhance peripheral nervous system (PNS) regeneration in vivo (see, Kerns et al. (1986) Soc. Neurosci. Abstr. Vol. 12, pp. 13) and central nervous system (CNS) regeneration (see, European Patent Application Pub. No. 261,833 by Zanakis et al.). However, such devices are bulky, typically requiring an external power supply and electrode leads penetrating through the skin and, therefore, are difficult to maintain.
Moreover, the effectiveness of such electric current-generating devices for nerve regeneration over a gap produced by resection (i.e., removal) of a nerve segment has not been demonstrated, and their effectiveness for regeneration of transected (i.e., cut) nerves has been questioned recently. See, for example, a study by M. E. McGinnis, Abstract No. 479.2, The Society for Neuroscience 20th Annual Meeting (1990) St. Louis, Mo., in which an attempt was made to repeat the experiments reported by Zanakis and others without success. In the McGinnis study, a silicone tube with electrodes at each end was used as a nerve guidance channel. The application of a current from one electrode to another for 12 days led to no difference in neurofilament positive profiles, or myelinated or unmyelinated nerve fiber density.
There exists a need for more effective nerve guidance channels which would enable the restoration of motor and/or sensory function. Materials and methods for nerve repair that would minimize surgical trauma, maximize the distance over which nerve cell processes will regenerate and the amount of neural tissue regrowth, prevent interference with nerve growth by scar tissue, and improve the chances for successful recovery of sensory or motor function. This would satisfy a long-felt need in this field.